DESCRIPTION: (Adapted from the Investigators abstract): The proposed research investigates functional interactions between the influenza A and B NS1 proteins with specific cellular proteins during viral infection. The NS 1 protein is a non-structural protein that for type A viruses regulates events post-transcription. The function(s) of the NS lB protein remains unclear. Recent advances in reverse genetics allow influenza A and B viruses to be generated entirely from cloned cDNAs. This is a powerful tool for the generation of mutant influenza viruses and the investigation of protein interactions that occur during the course of influenza infection. The proposed research utilizes this technique as well as GST pull-downs, affinity chromatography, and mutation and deletion analysis to identify specific cellular proteins that interact with the NS 1 protein. These protein interactions will provide insight that could allow for the development of more effective influenza antiviral therapies. Specific aims are: 1) Identify functional interactions between specific cellular proteins and the NS 1A protein of influenza A virus, with emphasis on identifying the function of this interaction with SRp54. The protein-binding site will be identified and the function of this specific protein interaction analyzed. 2) Identify functional interactions between specific cellular proteins and the NS lB protein of influenza B virus. The protein-binding sites will be identified and the function of these specific protein interactions analyzed. Emphasis will be on the interaction between NS lB and ISG15.